title: Steady-state metabolite concentrations reflect a balance between maximizing enzyme efficiency and minimizing total metabolite load.
abstract: Steady-state metabolite concentrations in a microorganism typically span several orders of magnitude. The underlying principles governing these concentrations remain poorly understood. Here, we hypothesize that observed variation can be explained in terms of a compromise between factors that favor minimizing metabolite pool sizes (e.g. limited solvent capacity) and the need to effectively utilize existing enzymes. The latter requires adequate thermodynamic driving force in metabolic reactions so that forward flux substantially exceeds reverse flux. To test this hypothesis, we developed a method, metabolic tug-of-war (mTOW), which computes steady-state metabolite concentrations in microorganisms on a genome-scale. mTOW is shown to explain up to 55% of the observed variation in measured metabolite concentrations in E. coli and C. acetobutylicum across various growth media. Our approach, based strictly on first thermodynamic principles, is the first method that successfully predicts high-throughput metabolite concentration data in bacteria across conditions.
authors.affiliation: Department of Computer Science, Technion-IIT, Haifa, Israel.
authors.forename: Naama
authors.initials: N
authors.lastname: Tepper
authors.forename: Elad
authors.initials: E
authors.lastname: Noor
authors.forename: Daniel
authors.initials: D
authors.lastname: Amador-Noguez
authors.forename: Hulda S
authors.initials: HS
authors.lastname: Haraldsdóttir
authors.forename: Ron
authors.initials: R
authors.lastname: Milo
authors.forename: Josh
authors.initials: J
authors.lastname: Rabinowitz
authors.forename: Wolfram
authors.initials: W
authors.lastname: Liebermeister
authors.forename: Tomer
authors.initials: T
authors.lastname: Shlomi
mesh_terms: D046969:Clostridium acetobutylicum / Q000378:metabolism*; D019295:Computational Biology / Q000379:methods; D004798:Enzymes / Q000378:metabolism*; D004926:Escherichia coli / Q000378:metabolism*; D053858:Metabolic Networks and Pathways / Q000502:physiology*; D055442:Metabolome / Q000502:physiology*; D008954:Models, Biological; D013816:Thermodynamics
chemical_list: D004798:Enzymes